1. Field of the Invention
This invention relates to methods of inhibiting leukotriene biosynthesis. In another aspect this invention relates to methods of treating diseases mediated by leukotrienes. In yet another aspect this invention relates to pharmaceutical compositions for inhibiting leukotriene biosynthesis.
2. Description of the Related Art
Arachidonic acid, a component of phospholipids found in cell membranes, is metabolized through an array of enzymatic pathways to afford biologically active metabolites including the leukotrienes. The leukotrienes are very potent substances, producing a variety of biological effects when present in the nanomolar or picomolar concentration range. They have been implicated in a variety of disease states. For example, Leukotriene C.sub.4 and Leukotriene D.sub.4 are potent constrictors of human airway smooth muscle. Aerosol administration of these substances to nonasthmatic volunteers induces bronchoconstriction. Leukotriene B.sub.4 is a potent chemotactic factor for inflammatory cells such as polymorphonuclear leukocytes. Leukotriene B.sub.4 has been found in the synovial fluids of rheumatoid arthritis patients and in psoriatic lesions. Leukotrienes have also been implicated as important mediators in allergic rhinitis, adult respiratory distress syndrome, inflammatory bowel disease, ischemic induced myocardial injury, reperfusion injury, gout, asthma, psoriasis, stroke, spinal cord injury and traumatic brain injury.